Pharmaceutical Manufacturing Handbook: Production and

RELEASE OF DRUGS FROM CONTROLLED-RELEASE DOSAGE FORMS 383
are then sealed with a waterproof material. A cathode is also required for the electrochemical
reaction to take place, and the cathode is usually made of the same
conductive material as the anode to simplify the fabrication procedure. The device
is submerged in an electrolyte solution containing ions and upon electric stimulation
forms a soluble complex with the anode in its ionic form. When release is desired,
an electric potential is applied between an anode membrane and a cathode, and the
gold membrane anode is dissolved within 10 – 20 s and allows the drug in the reservoir
to be released. This electric potential causes oxidation of the anode material to
form a soluble complex with the electrolytes which when dissolves allowing release
of the drug. Complex release patterns (such as simultaneous constant and pulsatile
release) can be achieved from the microchips. The microchip has the ability to
control both release time and release rate. The rate of release from a reservoir is a
function of the dissolution rate of the materials in the reservoir, the diffusion rate
of these materials out of the reservoir, or both. Therefore, the release rate from an
individual reservoir can be tailored to a particular application by proper selection
of the materials placed inside the reservoir [e.g., pure drug(s), drugs with polymers]
[124, 125] .
A microchip with insulin - fi lled reservoirs could eventually provide a better alternative
for the treatment of insulin - dependent diabetes mellitus (IDDM) [125] .
Because the microchip is capable of being programmed as well as integrated with
other electronic devices, it is supposable that the microchip could be incorporated
into a closed - loop biofeedback system. An electronic apparatus that continuously
measures the blood glucose levels could provide the stimulus to the microchip and
result in release of insulin into the bloodstream. Although such a system could still
not perfectly mimic an endogenous system of healthy person, it could practically
meet the needs of IDDM patients. Pulsatile release of synthetic gonadotropin –
releasing hormone (GnRH) can be achieved with a programmed microchip. A subcutaneous
implanted microchip containing 1000 drug reservoirs would be adequate
to administer a month ’ s worth of drug therapy. The implanted microchip would be
a convenient means to achieve the desired pharmacotherapeutic outcome of ovulation
without interfering with the patient ’ s daily activities or causing phlebitis.
While microchip drug delivery would be the most technologically advanced
delivery system, it has itself limited storage capacity for therapeutic drugs [125] .
Because most applications of this technology require implantation within bodily
tissues, the question arises, “ What would be done when the chip runs out of drug? ”
Some sort of procedure would be required to retrieve the empty chip cartridge once
it has emptied. Due to the limited quantity of drug that can be stored on one
chip, this technology is only ideal for potent drugs. If a larger dose of a medication
is required, the chip would not be adequate for dispensing larger quantities
of drug.
Magnetically Induced Release Magnetic carriers receive their magnetic response
to a magnetic fi eld from incorporated materials such as magnetite, iron, nickel, and
cobalt. For biomedical applications, magnetic carriers must be water based, biocompatible,
nontoxic, and nonimmunogenic. Earlier, Langer et al. [128] embedded magnetite
or iron beads into a drug - fi lled polymer matrix and then showed that they
could activate or increase the release of the drug from the polymer by moving a
magnet over it or by applying an oscillating magnetic fi eld. When the frequency of